Aryl mercury carboxylates of dyes



Patented Get. 26, 1937 STAT S PATENT Carl N. Andersen, Water-town, Mass,assignor to Lever Brothers Company, a corporation of Maine No Drawing.Application January 21, 1935, Serial No. 2,760

9 Claims. (o1. 26013) The present invention relates to the production ofcertain new organic mercury compounds, and more particularly to aromaticmercury derivatives of dyes containing a carboxyl group.

It is an object of my invention to produce new organic mercury compoundsuseful as germicides and for other therapeutic purposes.

More particularly, it is an object of my inven tion to prepare certainorganic mercury compounds which may be regarded as derivatives of dyes.

I have discovered that when certain hydrogen atoms in a dye are replacedby the essential radical of certain aromatic mercury compounds,compounds are produced which have extraordinarily high potency asantiseptics and germicides and at the same time are characterized byrelatively low toxicity and other desirable properties.

The compounds constituting the subject-matter of my invention may bedescribed as having the general formula (RI-IgMR in which R. representsan aromatic structure, to a carbon of which the mercury is directlyattached; in which a: is an integer representing the number of aromaticmercury groups in the compound, which integer is at least one and notmore than the number of replaceable hydrogen atoms in the radical R1;and in which R1 represents a radical of a dye, which radical is linkedto the RI-Ig group or groups through the replac ment of one or morehydrogen atoms in the dye. While the words group or groups are usedhereinafter, it is obvious that these words are to be understood assingular or plural depending upon the value of x.

More particularly, It represents an aromatic structure, which may be anaromatic nucleus with or without side chains, and the expressionaromatic structure used herein is intended to be generic and include anaromatic nucleus with or without side chains. The aromatic structure isof the type in which none of the nuclear or side chain carbon atoms hasdirect linkage with any element other than hydrogen, carbon or mercury.B may stand for the phenyl group, CcHs, or for an aromatic hydrocarbonhaving a nucleus similar to the phenyl hydrocarbons, as for example,polycyclic hydrocarbons, in which all of the nuclear carbon atoms, otherthan the one attached to mercury, and any side chain carbon atoms, havetheir valences satisfied either by carbon or hydrogen. Examples are thediphenyl, tolyl, xylyl, and naphthyl groups.

More particularly, R1 represents a radical of a dye which contains theCOOH group;

The dyes from which aromatic mercury derivatives may be prepared are ofvarious chemical structures, colorsand dyeing properties. I haveinvestigatedidyes of many chemical structures, such as the azo (mono andpoly) type, xanthine type, pyrazolcne type, azine type, anthraquinonetype, thiazole type, stilben type, quincline type, oxazine type,triphenyl methane type, anthraquinoid type, etc., all of which I findmay be used to produce aromatic mercury derivatives possessinggermicidal properties. By the term dye I refer to a chemical compoundcontaining one or more of the chromophore groups, and therefore to acompound possessing a characteristic color.

The chemical structure of dyes is very complex and the exact chemicalmechanism of the reactions into which they enter is very difiicult todetermine. In the following paragraphs I have outlined some generalprinciples which should assist in determining the formulae of my novelcompounds. However, having disclosed the method by which my newcompounds may be. produced so as to enable a person skilled in the artto practice my invention, I'do not feel obliged to assign a definitechemical formulato every compound within the scope of my invention.

Many dyes possess certain groups which contain a replaceable hydrogenatom. For example, the sulphonic group --SO3H, the carboxyl group -COOH,the hydroxyl group 'OI-I, the sulfonamido group SO2NH2, and the NI-Igroup. From my investigations I am inclined to believe that when a dyecontains one or more of any of these groups it is the hydrogen atom oratoms thereof that are replaced by the aromatic mercury radical.

In cases in which more than one of the different groups occur in onedye, it is difficult to tell in which group the hydrogen has beenreplaced by the aromatic mercury radical. Certain general rules shouldapply. There are exceptions to these rules due to the effect of sterichindrance, and the effect of other groups in the molecule. However, itis a convenient guide to classification. The sulfonic acid group is themost acidic and when present in a dye it will usually be the group toreact with the aromatic mercury compound. When the dye does not containa sulfonic group,

the carboxyl group is the next most acidic and mentioned more activegroups are absent or do not exist in the free state. The rule regardingthe dyes containing the NH group holds true with less regularity,however, as I find some instances Where the NH group is quite reactive.This is particularly true of dyes in which the reactivity of the NHgroup varies greatly with the surrounding groups. The difference inreactivity between the hydroxyl and NH groups is not as .pro-

nounced as is the case with the other groups, for

example, the carboxyl and the hydroxyl.

When it is desired to replace aparticular hydrogen atom by the aromaticmercury radical, it is often necessary to block the substitution in themore reactive groups. For'example, when a dye contains both the carboxyland the sulfonic groups and both are free acids, the aromatic mercuryradical will react with the sulionic group as explained above. Ifsufiicient alkali is added to convert the sulfonic group to an alkalisulfonate leaving the carboxyl group 'free, then the aromatic mercuryradical will react with the carboxyl group. Similarly, when only thecarboxyl and hydroxyl groups are free, the aromatic mercury radicalreacts with the carboxyl group. If the carboxyl group is converted intoa salt, the aromatic mercury radical will react with the hydroxyl group.The same system of blocking may be employed in the case of dyescontaining other combinations of the above mentioned radicals.

In many cases the dyes are sold as salts, in which case the hydrogen ofone or more groups has been replaced by an alkali metal. When the.dye-stuii is available only in this form, and it is desired tointroduce'the aromatic mercury radical into one of these groups, thefree acid should be liberated by treatment with a mineral acid beforebeing reacted with the aromatic mercury compound. a

If the dye is not so'treated the substitution will .no doubt takeplacein the most reactive group 'COONa, and the OH groups, it would bepossible to form three compounds, depending on the position in the dyemolecule at which the aromatic mercury radical is introduced.

The hydrogen atom of more than one of similar or different groups may bereplaced if desired. For example, if the dye contains two COOH groups ora COOH group and an OH group, the

. hydrogen of both groups may be replaced if a sufiicient quantity ofthe aromatic mercury compound is employed in the process. a

From the above explanation it will be apparent that when a dyecontaining the COOH group either naturally or by treatment of an alkalicarboxylate with an acid, the aromatic mercury radical'will be attachedto this group even though the dye contains one or more of the followinggroups: SO3Na, ONa, OH and NH. The dye, however, may not'contain theSO3H group.

The follo'wingexamples will illustrate the types of dyes which I mayemploy in producing the novel aromatic mercury compounds constitutingthe present invention:

Fastusol Yellow GGA (azo type), Schultz, 7th ed., #341, Colour Index#346.

, stances water Chrysamine L (azo type), Schultz #419, Colour Index#410. V

Alizarine Yelllow '(azo type), Schultz #66, Colour Index #40.

Colour Index #883. V r

Rhodamine B (xanthine type) ,Schultz #864, Colour Index #749. a

The Fastusol Yellow GGA, listed above, has the following formula:

C O O Na NH 3 NH o o ONa The dyes above noted are examples of dyescontaining the COOH group or salt corresponding thereto. They maycontain one or more of the SOsNa, OH, ONa, or NH groups. Dyes whichcontain the COOH group in combination with the SOsI-I group are notlisted here inasmuch as they constitute a part of the subject-matter ofmy application Serial No. 2,759, filed January 21, 1935;

The general method of preparing my novel' compounds consists in reactingthe dye with an aromatic mercury compound of the above mentionedRHg't'ype. the reacting components are soluble may be used. The compoundresulting from the reac- -tion is often relatively insoluble as comparedwith the reacting components and upon its pre-.

mercury compounds isv selected as a reacting material, such as thehydroxide, or a soluble salt,

for example, the acetate or the lactate. The hydroxide has the advantagethat in mostinis j the only other compound formed, if any, and theresultant product may be more easily purified.

The following examples are given as illustrative of the method by whichall of the dye compounds of the present invention maybe prepared and theproducts prepared are illustrative of representative aromatic mercurydye derivatives falling within the scope of my invention:

Erample Any common solvent in which 7 is separated by filtration, washedwell with warm water and dried.

This dye contains a free carboxyl group, the hydrogen of which isbelieved to be replaced by the phenylmercury radical Rhodamine B has thefollowing formula:

(C2HshN- N(C2Ht)z01 C O OH Example 2 17.64 grams of phenylmercuryhydroxide is dissolved in 2 liters of water and heated until solution iscomplete. The solution is filtered to remove any insoluble material. Tothe filtrate is added 200 cc. of hot water containing 18.54 grams ofAlizarine Yellow (Schultz #66, Colour Index #40) and the mixture heated.for a few minutes, during which time reddish brown crystals separate.The mixture is allowed to stand and cool, after which it is filtered andthe precipitate washed well and dried.

This dye contains one carboxyl group and one hydroxyl group. When thecarboxyl group, is free the carboxyl' hydrogen atom will, it isbelieved, be replaced by the phenylmercury radical. This dye may also beobtained with the carboxyl group substituted. In that case the dye mustbe treated preliminarily with an acid if the substitution'is to be madein the carboxyl group.

Alizarine Yellow has the following formula:

Example 3 35.28 grams of phenylmercury hydroxide is dissolved in 2liters of water and heated until solution is complete. move anyinsoluble material. A solution of 500 cc. of alcohol containing 47.52grams of Phloxine RB (Schultz #888, Colour Index #774), is prepared andto it is added sufiicient concentrated sulphuric acid to convert thealkali substituted group, or groups, into the free acid. The filtrate ofthe phenylmercury hydroxide solution is then added to the dye solutionand the mixture heated to evaporate off the alcohol and insurecompletion of the reaction. On cooling a violet precipitate separates.The mixture is allowed to stand, after which it is filtered and theprecipitate washed well with warm water and dried.

This dye contains an alkali metal carboxylate group and the alkali metalalcoholate group. The sulphuric acid liberates the free carboxylic acidgroup, the hydrogen of which is believed to be replaced by thephenylmercury radical.

In each of the above examples the reacting materials are employed insubstantially theoretical quantities. In certain instances, if desired,an excess, say of the dye may be employed in order to assure thecomplete conversion of the aromatic mercury compound.

From the description of these specific examples it will be readilyapparent to one skilled in the The solution is filtered to reart howother dyes of the type above described may be reacted with an aromaticmercury compound to produce aromatic mercury dye derivatives.

The operativeness of the process is not found to depend in any degreeupon the temperature at which the reaction is effected. It is.convenient to use heat because it facilitates the solution of thereacting components and in some cases speeds the reaction, but theprocess can be carried out at any temperature, for example, roomtemperature. .The process may be carried out in any solvent in whichboth reacting components are soluble. Water is usually employed forreasons of convenience, but any other material which does not enter intothe reaction and in which the materials are soluble, may be used, forexample, one of the alcohols, acetone, or mixtures of these with eachother or with water.

All of the compounds produced as above described are characterized byextraordinarily high potency as germioides. Tests to determine theefiicacy of certain of them in killing B. typhosus and Staph. aureuswere carried on under the following conditions:

Aqueous solutions of varying dilutions from 1:10,000 upward untilkilling ceased, were made up.

These dilutions were employed in the conduct of the tests by thefollowing methods:

Circular 198, U. S. Dept. of Agriculture, Dec. 1931, described as F. D.A. method against Eberthella typhi (typhoid bacillus) at 37 C. and F. D.A. Special Method against Staph, aureus at 37 C.

As illustrative of the potency of the compounds, the killing power ofthe following compounds is given merely as illustrative:

The figures rep-resent the maximum dilutions at which killing in minutesresulted:

B. typhosus Staph. aureus Phenylmercury derivative of PhloxinePhenylmercury derivative of Rhodamme B- l: 30, 000

In addition to their high germicidal value, all of these compounds arecharacterized by relatively low toxicity. Because of these properties itis possible to use them in extreme dilutions and in many situationswhere known germicides, be cause of toxic or other undesired properties,can not be employed. They may be used externally and locally withsatisfactory results from the germicidal standpoint and without harmfuleffect to the body or its functions.

The compounds retain their germicidal activity when incorporated in soapand various menstrums employed in preparing germicidal compositions.

When these new compounds are to be used directly as germicides they maybe employed in aqueous or other solutions or they may be formed intovarious preparations such as mouth washes, tooth pastes, soaps,ointments, etc.

I claim:

1. A new organic mercury compound of the general formula (RHgmRi, inwhich R represents an aromatic structure, to a carbon atom of which themercury is directly attached, and in which none of the carbon atoms hasdirect linkage with any element other than hydrogen, carbon and mercury;in which R1 represents a radical of a dye containing a carboxyl group,which radical is linked to an RHg group by the replacement of a carboxylhydrogen atom; and in which .r, is an integer representing'the number ofRHg groups in the compound, which integer is at least one and not morethan the number of 'carboxyl hydrogen atoms 'in the radical R1.

2. A new organic mercury compound ofvthe general formula (RHghaRr, in.which R represents an aromatic structure, to a carbon atom of V whichthe mercury is directly attached; and in which none of the carbon atomshas direct linkage with any element other than hydrogen, carbcn andmercury; in which R1 represents a radical'of a dye containing carboxyl,hydroxyl and NH groups, which. radicalislinke'd to an RHg group by thereplacement. of a carboxyl hydrogen atom; and in which a; is an integerrepresenting the' number of RI-Ig groups in the compound, whichinteger-is at least one and'not more than the number of carboxylhydrogen atoms in the'radical R1.

3. A new organic mercurycompound of the generalformula (RHg)2.R1, inwhich R represents an aromatic structure, to a carbon atom of which themercury is directly attached, and in which none of the carbon atoms hasdirect'linkage with any element other than hydrogen, car- Icon andmercury; in which Ri'represents a radical of a dye containingcarboxyland hydroxyl groups, which radical is linked'to an RI-Ig groupby the replacement of a carboxyl hydrogen atom;

and in which a: is an integer representing the number of RHg groups inthe compound, which integer is at least one and not more than'the numberof carboxyl hydrogen atoms in the radical R1.

general formula (CsHsI-Ig) 1;.R1, in which R1 represents a radical of adye containing carboxyl, hydroxyl and NH groups, which radical is linkedto a C6H5Hg group by the replacement of a carboxyl hydrogen .atom; andin which at is an integer representing the number of CsHsHg groups inthe compound, which integer is at least one and not more than the numberof c'arboxyl hydrogen atoms in the radical R1.

I 6. A new organic mercury compound of the general formula (Ce-H5Hg)1.111, in which R1 represents a radical of a dye containing carboxyl andhydroxyl groups, which radical is linked to a CaHsHg group byreplacement of a carboxyl hydrogen atom; and inrwhich x'is an integerrepresenting the number of CsHsI-Ig groups in the compound, whichinteger is at least one and not more than the number of carboxylhydrogen atoms in the'radical R1.

7. Phenylmercury carboxylate of the dye Aliza- 7 rine Yellow, said dyehaving the formula: V

QOOOH v on 8.;Phenylmercury carboxylate'of the dye Rhodamine B, saiddyehaving the formula:

COOH

9. A phenylmercury carboxylate of the dye Fastusol Yellow GGA, said ,dyehaving the formula:

CARL N. ANDERSEN.

